Nitric Oxide ameliorates ischemia-reperfusion injury after rat lung transplantation / 中华器官移植杂志

ABSTRACT

Objective To investigate the effects of inhaled low dose nitric oxide(NO)on lung ischemia-reperfusion injury during flush and delayed 10 min after reperfusion.Methods Sixty health a- dult male Sprague-Dawley rats were randomly allocated to the control and the NO group.Before the donor lung was harvested,the right hilus was clipped for 5 min(clipping test),then blood sample was collected from carotid artery for arterial blood gas analysis as baseline.Lung transplantation was per- formed in a“cuff-like”vessel anastomosis technique.Dynamic compliance(Cdyn)and resistance of airway(Raw)were monitored before operation(baseline)and after 2-h reperfusion.The graft's gas exchange and oxygenation were assessed by“clipping test”after 2-h reperfusion.The lung graft was harvested for measuring wet/dry weight ratio(W/D),the activity of myeloperoxidase(MPO)and in- ducible nitric oxide synthase(iNOS),the content of malonyldialdehyde(MDA),and the expression of iNOS gene and protein.Results After 2-h reperfusion,compared to the control group,PaO_2/FiO_2, OI,and Qs/Qt were improved significantly in the NO group(277?91 vs.157?47,P＜0.01;2.67?0.89 vs.4.72?1.48,P＜0.01;21.1?4.57 vs.27.1?2.37,P＜0.01,respectively).The activi- ties of MPO were significantly reduced in NO group(1.80?0.46 vs 3.08?0.65 U/g tissue,P＜0.01).The content of MDA in the lung tissue of NO group was significantly higher than that of the control group(34.8?7.9 vs.20.0?11.2 nmol/mg protein,P＜0.05).Inflammatory cell infiltration was also significantly reduced(P＜0.05).The expression of iNOS gene and protein in the lung tissue of NO group was significantly lower than that of the control group.The activities of iNOS were also significantly reduced in NO group(10.6?10.2 vs 97.8?82.2 nmol?g~(-1)?min~(-1),P＜0.05).The im- munohistochemical positive staining of iNOS was localized in the alveolar epithelial cells and the in- flammatory cells infiltrated in the alveolar spaces and mesenchymal tissue.But there were no signifi- cant differences between two groups in Cdyn,Raw and W/D ratio.Conclusion Inhaled low dose NO might mitigate the intrapulmonary shunt,prevent neutrophil sequestration,inhibit the expression of iNOS gene and protein in isograft,thereby ameliorate ischemia-reperfusion injury and improve the ox- ygenation of the graft.